Clinical presentation of multiple myeloma and other
lymphoproliferative disorders is characterised, beyond specific
haematological signs and symptoms, by a broad spectrum of kidney
lesions. Differential diagnostics is the major challenge, demanding
pathology evaluation of kidney tissue, as different types of lesions,
mainly paraproteinemic, cannot be differentiated solely on the basis
of clinical features. Importantly, symptoms of kidney damage may
dominate over LPD symptoms, and even preclude overt LPD’s.

IgD myeloma is rare, but aggressive tumour, diagnosed
approximately in 2-2.5% cases of MM. Diagnostic problems arise from
the fact, that the routine test does not detect the M-spike in 60% of
patients, and when it is detected, the concentration is usually smaller
than 2g/dL. An overproduction of Light Chains (LC), usually λ, is found
in 90-96% of patients. The disease course is often accompanied by AL
amyloidosis and light chain proteinuria, renal failure is observed in
33% of cases at the moment of diagnosis.

The pathology pattern of renal damage in patients with
LPD, showing a combination of cast-nephropathy and light chain
deposition disease is also rare and reported in literature like single
cases or small series.

Clinical presentation of Multiple Myeloma (MM) and
other Lymphoproliferative Disorders (LPD) is characterized,
beyond specific haematological signs and symptoms, by a
broad spectrum of kidney lesions. Renal involvement is defined
by numerous mechanisms, but mainly by the deposition of
secreted paraproteins. Paraproteinemic lesions, in turn, may be
represented by organized (crystals, fibrils, microtubules), and
non-organized deposition of monoclonal immunoglobulin’s or fragments thereof, mostly light chains (LC). They may involve
the four components of the kidney parenchyma: glomeruli,
tubules, interstitium and blood vessels. Organized depositions
include Cast Nephropathy (CN), light-chain tubulopathy, AL/AH
amyloidosis, glomerulonephritis with an organized microtubular
monoclonal deposits, and cryoglobulinemic Glomerulonephritis
(GN). Non-organized deposition group comprise Light Chain/
Heavy Chain Deposition Disease (LCDD/HCDD), proliferative
GN with monoclonal deposits of IgG/IgA, and non-proliferative
GN with monoclonal deposits of IgM. It appears that amino acid
sequence of the monoclonal LC and other monoclonal proteins,
defining inherent biochemical properties, is the primary
determinant of the specific pattern of renal parenchymal
deposition and clinical disease. Patients may present with Acute
Kidney Injury (AKI), Nephrotic Syndrome (NS), proteinuria and/
or haematuria, arterial hypertension or chronic kidney disease.
Differential diagnostics is the major challenge, demanding
pathology evaluation of kidney tissue, as the above mentioned
lesions cannot be differentiated solely on the basis of clinical
features. Importantly, symptoms of kidney damage may dominate
over LPD symptoms, and even preclude overt LPD’s [1-13].

MM presents with end organ damage manifested as one or
more of the following –bone pain, kidney damage, impaired
haematopoiesis, hypercalcemia, and susceptibility to infections.
In laboratory tests MM typically manifests itself by the presence
of high paraprotein (mainly IgG, IgA and Bence-Jones) levels in
serum and urine. Sometimes, however, the clinical picture of MM
is quite different from the classic manifestation, which can cause
diagnostic difficulties, thereby delaying the treatment. One of
these rare and unusual forms of MM is IgD myeloma.

Plasma cell leukemia with IgD paraprotein was firstly
described in 1968, and since that time IgD myeloma remains rare,
but aggressive tumour, diagnosed approximately in 2-2.5% cases
of MM and affecting young people. Diagnostic problems arise
from the fact, that the routine test does not detect the M-spike
in 60% of patients, and when it is detected, the concentration
is usually smaller than 2g/dl. An overproduction of LC (Bence-
Jones paraprotein), usually λ, is found in 90-96% of patients.

The disease course is often accompanied by AL amyloidosis
and LC proteinuria, renal failure is observed in 33% of cases at
the moment of diagnosis. Lymphadenopathy is seen in 10% of
patients [14-21].

The pathology pattern of renal damage in patients with
LPD, showing a combination of cast nephropathy and LCDD is
also rare – such coexistence is reported in literature like single
cases or small series. At least two possible explanations for these
findings suggested so far. It was observed, that both fibrillar
and non-fibrillar monoclonal LC deposits may coexist in the
same patient, and the identity of the amino acid sequence of the
deposited protein has been reported. On the other hand, cases
with more than one pattern of LC deposition may be explained by
the biclonal proliferative process with more than one pathogenic
LC, causing damage. Again, only rare MM (2%) result in biclonal
gammopathy with the production of two different heavy chains
and/or light chains, with the combinations of IgG/IgM, IgA/
IgG, κ/λLC and IgD/IgM described in few reports, unfortunately
no data concerning influence of coexistence of two and more
patterns on renal outcome is available [22-30].

Here we present a case of IgD myeloma, manifested with the
combination of LCDD and cast nephropathy.

Caucasian Male, 52 Years Old, Admitted July 14, 2015

Main Complains: Weakness, dizziness, breath shortage, loin
pain.

Previous Medical History: In 1988 he was diagnosed
with hepatitis B, no treatment, no follow-up for many years. In
2010, his nose basalioma was removed in the outpatient clinic,
preoperative work-up was unremarkable.

He was seen by a local hematologist, diagnosis of multiple
myeloma was declined, and patient was diagnosed with "primary"
LCDD. Serum and urine immunochemistry were ordered, and the
patient was referred to our clinic for the second opinion.

Diagnostics Considerations, Treatment and Further
Work-Up: At that point we diagnosed AKI, and concluded that
the cause of AKI could be nothing but cast nephropathy on top
of LCDD in a patient with myeloma. Patient was urgently started
with hemodialysis and normal saline infusions, skeletal X-ray,
peripheral lymph nodes ultrasound, and bone marrow biopsy
were performed, and immunochemistry results ordered from
external lab, and kidney biopsy paraffin blocks were reprocessed
and re-evaluated.

Skeletal X-ray: Did not found any lesions.

Immunochemistry: Showed traces of paraprotein D-λ
and Bence-Jones-λ in serum, and urinary excretion of Bence-
Jones-λ 1.22g/day. Cryoglobulins were not found IgG, IgA and
κ/λ coefficients were below the normal range, CRP and β2-
microglobulin- significantly elevated.

Treatment and Follow-Up: Patient was seen by haematologist
and referred to haematology unit for chemotherapy. At the latest
evaluation (September15, 2015) patient receiving standard
chemotherapy per BCD (Bortezomib-Cyclophosphamide-
Dexamethasone) protocol, doing well, but still on hemodialysis.

Conclusions

Presented case demonstrates characteristic features
if IgD myeloma, like relatively young age, low grade IgD
paraproteinemia, overproduction of LC with LC-proteinuria,
lymphadenopathy and renal failure at presentation. Pathology
findings with typical picture of LCDD were misleading, and only
rapidly-progressive renal failure with kidney enlargement, not
consistent with LCDD natural course, demanded re-assessment
of kidney biopsy and more detailed work-up, which finally gave
a clue to the diagnosis. The pathology pattern of renal damage: a
combination of cast nephropathy and LCDD confirms the leading
role of cast-nephropathy in the clinical presentation with AKI,
dominating over other symptoms. According to our experience
such combined renal damage is rare, but not unique –in our
cohort of 139 patients with LPD and renal damage, confirmed by
pathology, we also have patients with AL amyloidosis and LCDD,
and with combination of cast nephropathy, AL amyloidosis and
LCDD. This case also illustrates the importance of renal damage
pattern, typical for MM, for diagnostics of this disease in patients
without clinical MM features.